Adolescents with Rett syndrome at critical care pathway junctures: Examining clinicians' decision to initiate invasive long-term ventilation.

BACKGROUND: The initiation of invasive long-term ventilation (I-LTV) for an adolescent with Rett Syndrome (RTT) involves many serious bioethical considerations. In moving towards a more inclusive model of patient participation, transparency surrounding the main influencing factors around this decision is important. OBJECTIVE: We aimed to identify the main drivers influencing a clinician's decision to support initiation of I-LTV for an adolescent with RTT. METHOD: We used an anonymous online vignette-based factorial survey. The survey was distributed internationally through eight professional multi-disciplinary organisations to reach clinicians working in paediatrics. RESULTS: We analysed 504 RTT vignettes completed by 246 clinicians using mixed effect regression modelling. The main three significant influencing factors identified were: parental agreement with the decision to support initiation, the family's support network, and proximity to a tertiary care centre. Additional comments from participants focused on family support, and the importance of on-going communication with the family. CONCLUSION: As the rights of those with disabilities improve and participation of adolescents in decision-making becomes more established, effective communications with the family around goals of care and particular sensitivity and reflective practice around methods of consensus building will likely contribute to a positive decision-making process at this difficult time.

The factorial survey as an approach to investigate clinical decision-making: examining influences on a clinician's decision to initiate life-sustaining clinical technology for a child with spinal muscular atrophy type 1.

Background: Spinal Muscular Atrophy (SMA) type 1 is a debilitating condition with a poor prognosis, though therapeutic advances are promising. Long-term ventilation is a common management strategy as respiratory function deteriorates. Without consensus on best practice respiratory management, the decision to initiate invasive LTV (I-LTV) for this group of young children involves many ethical considerations. Understanding the main influencing factors on a clinician's likelihood to initiative I-LTV for a child with chronic critical illness is important to maintain transparency and trust with the family during this challenging time. Methods: A factorial survey was used to identify the factors that influence a clinician to support initiation of I-LTV for children with SMA type 1. Factorial survey content was based on literature and evidence-based practice and the content was subject to extensive pretesting and pilot testing. An anonymous survey was disseminated (Oct 2021-Jan 2022), via eight international professional organisations, to clinicians with experience caring for children at the time of initiation of I-LTV. Results: 251 participants answered 514 vignettes on SMA type 1. The greatest influencing factor on clinician's likelihood to initiate I-LTV was parental agreement with the need to initiate I-LTV. Additional qualitative comments from participants support this finding. Clinicians also highlighted the important role of innovative therapies as well as the availability of supports for families when considering initiation however these findings were context based. Conclusions: The factorial survey approach provides a valuable way of identifying influencers on decision-making in sensitive situations. The findings demonstrate the acceptance of the centrality of parental influence in decisions on care delivery. Effective communication with the child's family is key to ensuring shared understanding and agreement of goals of care. More international research is needed on the long-term effects of novel treatments, as well as impact on quality of life and influence of geographical location, to inform decision-making.

Impact of adapting paediatric intensive care units for adult care during the COVID-19 pandemic: a scoping review.

OBJECTIVES: The objectives were to categorise the evidence, map out the existing studies and explore what was known about the organisation of paediatric intensive care units (PICUs) during the first 18 months of the COVID-19 pandemic. Additionally, this review set out to identify any knowledge gaps in the literature and recommend areas for future research. DESIGN: Scoping review. METHODS: This study used Arksey and O'Malley's six-stage scoping review framework. A comprehensive search was conducted using the following databases, CINAHL Complete; MEDLINE; PsycINFO; PsycARTICLES and EMBASE and grey literature search engines. A search strategy with predefined inclusion criteria was used to uncover relevant research in this area. Screening and data collection were done in duplicate. RESULTS: 47 631 articles were obtained through searching. However, only 25 articles met the inclusion criteria and were included in the analysis. Three dominant themes emerged from the literature: (1) the reorganisation of space for managing increased capacity; (2) increased staffing and support; and (3) the resulting challenges. CONCLUSION: COVID-19 has strained institutional resources across the globe. To relieve the burden on intensive care units (ICUs), some PICUs adjusted their units to care for critically ill adults, with other PICUs making significant changes, including the redeployment of staff to adult ICUs to provide extra care for adults. Overall, PICUs were collectively well equipped to care for adult patients, with care enhanced by implementing elements of holistic, family-centred PICU practices. The pandemic fostered a collaborative approach among PICU teams and wider hospital communities. However, specific healthcare guidelines had to be created to safely care for adult patients.

Technology solutionism in paediatric intensive care: clinicians' perspectives of bioethical considerations.

BACKGROUND: The use of long-term life-sustaining technology for children improves survival rates in paediatric intensive care units (PICUs), but it may also increase long-term morbidity. One example of this is children who are dependent on invasive long-term ventilation. Clinicians caring for these children navigate an increasing array of ethical complexities. This study looks at the meaning clinicians give to the bioethical considerations associated with the availability of increasingly sophisticated technology. METHODS: A hermeneutic phenomenological exploration of the experiences of clinicians in deciding whether to initiate invasive long-term ventilation in children took place, via unstructured interviews. Data were analysed to gain insight into the lived experiences of clinicians. Participants were from PICUs, or closely allied to the care of children in PICUs, in four countries. RESULTS: Three themes developed from the data that portray the experiences of the clinicians: forming and managing relationships with parents and other clinicians considering, or using, life sustaining technology; the responsibility for moral and professional integrity in the use of technology; and keeping up with technological developments, and the resulting ethical and moral considerations. DISCUSSION: There are many benefits of the availability of long-term life-sustaining technology for a child, however, clinicians must also consider increasingly complex ethical dilemmas. Bioethical norms are adapting to aid clinicians, but challenges remain. CONCLUSION: During a time of technological solutionism, more needs to be understood about the influences on the initiation of invasive long-term ventilation for a child. Further research to better understand how clinicians, and bioethics services, support care delivery may positively impact this arena of health care.

An Evaluation of the Use of Low-Fidelity and High-Fidelity Mannequins in Clinical Simulations in a Module Preparing Final Year Children's and General Nursing Students for Internship Placement.

Internationally, the use of simulation-learning environments in nursing education has escalated over the last number of years. Simulations have been recognized as providing clinical opportunities for student nurses to gain experience in a safe and controlled learning environment. A module specifically preparing fourth year children's and general nursing students for internship was developed. Preparation work for these simulation sessions included a video for the students to watch which demonstrated evidence-based care using sample simulations. This research aims to evaluate two simulation scenarios, using low-fidelity and high-fidelity mannequins for children's nursing students as part of a nursing module preparing them for internship practice placement. This mixed-methods evaluation survey of students was conducted in one School of Nursing in a Higher Education Institute in Ireland in the academic year 2021-2022. A simulated learning package was created using a partnership approach with members from the Higher Education Institute and the clinical learning site and piloted with 39 students. This was evaluated using an anonymous, online questionnaire with 17 student responses. An ethical exemption was granted for this evaluation. All students reported the use of the simulations, including the pre-simulation video as beneficial to enhance their learning and to prepare them for internship. The use of low-fidelity and high-fidelity mannequins enhanced their learning process. Students recommended implementing further simulations throughout their programme to enhance their learning experiences. The findings of this evaluation can provide guidance to aid future development of interactive simulations in preparing students for practice placements. Both low fidelity and high fidelity have their places in simulation and education, depending on the scenario and associated learning outcomes. Collaboration between academia and clinical practice is crucial, to bridge the theory-practice gap and demonstrate a positive relationship between staff in both settings.

Integrated care for children living with complex care needs: an evolutionary concept analysis.

Children with complex care needs (CCNs) are in need of improved access to healthcare services, communication, and support from healthcare professionals to ensure high-quality care is delivered to meet their needs. Integrated care is viewed as a key component of care delivery for children with CCNs, as it promotes the integration of healthcare systems to provide family and child-centred care across the entire health spectrum. There are many definitions and frameworks that support integrated care, but there is a lack of conceptual clarity around the term. Furthermore, it is often unclear how integrated care can be delivered to children with CCNs, therefore reinforcing the need for further clarification on how to define integrated care. An evolutionary concept analysis was conducted to clarify how integrated care for children with CCNs is defined within current literature. We found that integrated care for children with CCNs refers to highly specialised individualised care within or across services, that is co-produced by interdisciplinary teams, families, and children, supported by digital health technologies.  Conclusion: Given the variation in terms of study design, outcomes, and patient populations this paper highlights the need for further research into methods to measure integrated care. What is Known: • Children with complex care needs require long-term care, and are in need of improved services, communication, and information from healthcare professionals to provide them with the ongoing support they need to manage their condition. • Integrated care is a key component in healthcare delivery for children with complex care needs as it has the potential to improve access to family-centred care across the entire health spectrum. What is New: • Integrated care for children with CCNs refers to highly specialised individualised care within or across services, that is co-produced by interdisciplinary teams, families, and children, supported by digital health technologies. • There is a need for the development of measurement tools to effectively assess integrated care within practice.

Organisation of care in paediatric intensive care units during the first 18 months of the COVID-19 pandemic: a scoping review protocol.

INTRODUCTION: The emergence of COVID-19 has had a significant impact on hospital services, particularly care delivered to those in intensive care units (ICUs) and paediatric ICUs (PICUs) across the world. Although much has been written about healthcare delivery and the healthcare setting since COVID-19 began, to the authors' knowledge, this is the first scoping review to investigate the organisation of care and changes implemented in PICUs during the COVID-19 pandemic. The aim is to conduct a scoping review of the literature to map out the existing studies about care delivery in PICUs during the COVID-19 pandemic and the changes made to the organisation of care in these units during the first 18 months of the pandemic. This review will also identify gaps in current knowledge in this area. METHODS AND ANALYSIS: This study will be guided by the Joanna Briggs Institute's methodology for scoping reviews, using Arksey and O'Malley's six-stage scoping review framework: (1) identifying the research question; (2) identifying relevant studies; (3) selecting the studies; (4) data charting; (5) collating, summarising and reporting results; and (6) consulting with experts. A comprehensive search will be conducted using the following databases: CINAHL Complete; MEDLINE; PsycINFO; PsycARTICLES and EMBASE. A search strategy with predefined inclusion and exclusion criteria will be used to uncover relevant research in this area. This study will include quantitative, qualitative and mixed research methods studies published in English from 2019 to May 2021. ETHICS AND DISSEMINATION: Ethical approval is not required for this scoping review. The results from this study will be disseminated through conferences and in peer-reviewed academic journals for those working in the healthcare arena.

Virtual reality device to improve the tolerability of lumbar puncture.

Background: Virtual reality is increasingly being used as an adjunct or replacement to pharmacological analgesia and sedation during medical procedures. Methods and results: We report the successful use of a virtual reality device in a highly anxious patient undergoing lumbar puncture. Conclusion: The case demonstrates how virtual reality technology may benefit patients undergoing invasive procedures such as lumbar puncture. Virtual reality may, therefore, offer an alternative or adjunct to sedation and analgesia and may reduce the amount of pharmacological therapy required.

The Meaning Given to Bioethics as a Source of Support by Physicians Who Care for Children Who Require Long-Term Ventilation.

The role and potential of bioethics input when a child requires the initiation of technology dependence to sustain life is relatively unknown. In particular, little is understood about the meaning physicians give to bioethics as a source of support during the care of children in pediatric intensive care who require long-term ventilation (LTV). We used a hermeneutic phenomenological approach to underpin the collection and analysis of data. Unstructured interviews of 40 physicians in four countries took place during 2020. We found that elements of trust, communication and acceptance informed the physicians' perceptions of the relationship with bioethics. These ranged from satisfaction to disappointment with their input into critical decisions. Bioethics services have potential to help physicians gain clarity over distressing and complex care decisions, yet physicians perceive the service inconsistently as a means of support. This research provides a sound basis to guide more beneficial interactions between clinicians and bioethics services.

Enhancing care of children with complex healthcare needs: an improvement project in a community health organisation in Ireland.

BACKGROUND: Integration of care for children with complex care needs is developing slowly internationally. There remains wide variation in the governance of, and access to, care for these children and their families. LOCAL PROBLEM: There was a need to develop a service that would have a specific remit for organising the overall management and governance of the care of these children in the community. METHOD: A bespoke model was established specifically to support the needs of children with complex healthcare needs (CHNs). The sole focus of the team is to provide the highest standard of care to these children and their families, and to enable families to remain central to decision-making. INTERVENTION: The service for children with CHNs was established in August 2017 with the appointment of a service manager and case managers. A comprehensive training and education programme was put in place to support care to the children and their families. RESULTS: The service is viewed as delivering high-quality care. Parents and stakeholders highlighted the value placed within the service on individualised care, specialist knowledge and the importance of advocacy. CONCLUSIONS: The model recognises the exceptional lives these children and families live, given the complexities and challenges they have to overcome on a daily basis. The team have built a specialist knowledge and skill set in supporting families and others involved in the care of the child, as they are solely employed and dedicated to the provision of care to children with CHNs. The corporate governance structures seem strong and stand up to scrutiny very well in terms of parents' and stakeholders' perspectives and in the context of published international best practice.

Respite Care for Children with Complex Care Needs: A Literature Review.

Children with complex care needs form a diverse population with a variety of health and social care requisites in the presence of a range of complex symptoms and diagnoses. An exploratory literature review with a systematic search of the current qualitative literature was undertaken to explore parents' perceptions and evaluation of respite care services for children with complex needs. A systematic search was undertaken using a pre-defined search strategy in six databases; CINAHL, EMBASE, PsycINFO, Applied Social Sciences Index & abstracts and Web of Science. Studies were screened using inclusion criteria and eight studies were included in the review. These were analyzed using thematic analysis based on Braun and Clarke framework. Findings identified that there was a limited availability of respite care services for children with complex needs. Parents' perceived that respite was beneficial for themselves, their child and other siblings in the family. Barriers to accessing respite were also identified. It is recommended that respite services should be flexible and appropriate to the family's needs. A combination of in home and out of home services that are responsive to families' needs and are flexible would be optimal. Qualitative research is considered most suitable to obtain the views of parents of children with complex needs. Further research is recommended in this area, particularly in determining how services may improve and what the views of children using the respite services and their siblings are regarding respite.

The effects of COVID-19 on IBD prescribing and service provision in a UK tertiary centre.

BACKGROUND: To quantify the effects of COVID-19 on our inflammatory bowel disease (IBD) unit, including service provision, prescribing practices and use of therapeutic drug monitoring (TDM). METHODS: We performed a single centre retrospective observational cohort study. Data was extracted from our IBD database, electronic patient records and radiology/endoscopy reporting systems between 16/3/20-17/4/20 and the corresponding period in 2019. RESULTS: A similar number of patients commenced biologic therapy before COVID-19 (n = 37) and during the pandemic (n = 36). Patients in the pre-COVID-19 cohort were older (median 36 vs 29 years, P = 0.009) with a longer median disease duration (9.3 vs 5.2 years, P = 0.02). During COVID-19 there was a nonsignificant increase in prescribing of vedolizumab (8/37, 22% vs 14/36, 39%, P = 0.13) and a higher proportion of patients were anti-TNF-naïve (3/17, 18% vs 18/24, 74%, P = 0.0004). There was a reduction in use of concomitant immunomodulators (22/29, 76% vs 4/34, 12%, P < 0.0001) and increased biologic use in thiopurine-naïve patients (3/37, 8% vs 15/36, 42%, P = 0.001). Use of TDM fell by 75% (240 vs 59 tests). Outpatient appointments fell by 68% and were conducted via telemedicine. MRI scanning, endoscopy, luminal surgery and inpatient numbers fell by 87%, 85%, 100% and 82% respectively. IBD Clinical Nurse Specialist and Pharmacist helpline contacts increased by 76% and 228% respectively. CONCLUSIONS: We observed prescribing differences during COVID-19, bypassing the initiation of immunomodulators and/or anti-TNF therapy in favour of vedolizumab with a reduction in immunomodulator prescribing. We also observed a rapid reorganisation of service provision, including a shift towards telemedicine and online solutions.

Well siblings' experiences of living with a child following a traumatic brain injury: a systematic review protocol.

BACKGROUND: The aim of this systematic review is to synthesize the available evidence identified through a systematic search on well siblings' experiences of living with a child following a traumatic brain injury (TBI). Brain injuries in children have been referred to as the "silent epidemic" of current times. Brain injuries in children are also recognized as a global public health concern, with the impact on children, effects on family life, and caregiving markedly misunderstood and underestimated. It is widely recognized that a serious brain injury impacts on the whole family, both immediate and extended regardless of the age of the individual who experiences the brain injury. While some research refers to parental experiences of children with TBIs and caregivers experiences, there is a dearth of literature relating to the impact on well siblings and their perspectives. Well siblings' experiences regarding the impact of living with a child post-TBI are not well understood. In order to advance the delivery of family nursing care in the home, an understanding of the well siblings' experiences is fundamental. METHODS: The search will be conducted using seven medical and healthcare databases for articles published up until February 2019. Two reviewers will independently screen the articles for inclusion and assess for study quality using the standardized critical appraisal instrument from the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI). Two reviewers will extract data from each study and carry out data analysis to uncover themes within the literature. Data synthesis of findings will be carried out using JBI-QARI. DISCUSSION: It is anticipated that the findings of the proposed review will be of interest to health and social care professionals, particularly those working in units where children have suffered TBIs, their well siblings, and families. The aim is to identify well siblings' experiences which can inform enhanced care delivery to the families of children following a TBI. The findings of this review will provide evidence to aid professionals with the assessment of siblings' needs to enhance their sense of self within the family unit. Future directions, in addition to potential limitations of the approach, will be discussed. SYSTEMATIC REVIEW REGISTRATION: PROSPERO 2018 CRD42018111036.

Deriving a water quality guideline for protection of aquatic communities exposed to triclosan in the Canadian environment.

Triclosan is an antibacterial and antifungal chemical used in a variety of consumer products, including soaps, detergents, moisturizers, and cosmetics. Aquatic ecosystems may be exposed to triclosan following the release of remaining residues in wastewater effluents and biosolids. In December 2017, Environment and Climate Change Canada (ECCC) released a federal environmental quality guideline (FEQG) report that contained a federal water quality guideline (FWQG) for triclosan. This guideline will be used as an adjunct to the risk assessment and risk management of priority chemicals identified under the Government of Canada's Chemicals Management Plan (CMP). The FWQG value for triclosan (0.47 µg/L) was derived by ECCC using a hazardous concentration for 5% of species (HC5) from a species sensitivity distribution (SSD). We recalculated the FWQG after performing an independent analysis and evaluation of the available aquatic toxicity data for triclosan and compared our results with the ECCC FWQG value. Our independent analysis of the available aquatic toxicity data entailed conducting a literature search of all available and relevant studies, evaluating the quality and reliability of all studies considered using thorough and consistent study evaluation criteria, and thereby generating a data set of high-quality toxicity values. The selected data set includes 22 species spanning 5 taxonomic groups. An SSD was developed using this data set following the ECCC approaches. The HC5 from the SSD derived based on our validated data set is 0.76 µg/L. This HC5 value is slightly greater (i.e., less sensitive) than the value presented in ECCC's final FWQG. Integr Environ Assess Manag 2018;14:437-441. © 2018 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Organophosphate triesters and selected metabolites enhance binding of thyroxine to human transthyretin in vitro.

The toxicological properties of organophosphate (OP) triesters that are used as flame retardants and plasticizers are currently not well understood, though increasing evidence suggests they can affect the thyroid system. Perturbation of thyroid hormone (TH) transport is one mechanism of action that may affect thyroid function. The present study applied an in vitro competitive protein binding assay with thyroxine (T4) and human transthyretin (hTTR) transport protein to determine the potential for the OP triesters, TDCIPP (tris(1,3-dichloro-2-propyl) phosphate), TBOEP (tris(butoxyethyl) phosphate), TEP (triethyl phosphate), TPHP (triphenyl phosphate), p-OH-TPHP (para-hydroxy triphenyl phosphate), and the OP diester DPHP (diphenyl phosphate), to competitively displace T4 from hTTR. Enhancement of T4 binding to hTTR, rather than the hypothesized competition, was observed for the six OP esters and in a concentration-dependent manner. For example, T4-hTTR binding was significantly increased at concentrations of TBOEP as low as 64 nM, and up to 184% of controls at 5000 nM. A plausible explanation of these results, which to our knowledge has not been previously reported, may be allosteric interactions of the OP esters with hTTR allowing T4 to access the second site of the TH binding pocket. These in vitro results suggest a novel mechanism of OP ester toxicity via T4 binding enhancement, and possible dysregulation of T4-hTTR interactions.

In Vitro and in Silico Competitive Binding of Brominated Polyphenyl Ether Contaminants with Human and Gull Thyroid Hormone Transport Proteins.

Tetradecabromo-1,4-diphenoxybenzene (TeDB-DiPhOBz) is a highly brominated additive flame retardant (FR). Debrominated photodegradates of TeDB-DiPhOBz are hydroxylated in vitro in liver microsomal assays based on herring gulls (Larus argentatus), including one metabolite identified as 4″-OH-2,2',2″,4-tetrabromo-DiPhOBz. Chemically related methoxylated tetra- to hexabromo-DiPhOBzs are known contaminants in herring gulls. Collectively, nothing is currently known about biological effects of these polybrominated (PB) DiPhOBz-based compounds. The present study investigated the potential thyroidogenicity of 2,2',2″,4-tetrabromo-(TB)-DiPhOBz along with its para-methoxy (MeO)- and hydroxy-(OH)-analogues, using an in vitro competitive protein binding assay with the human thyroid hormone (TH) transport proteins transthyretin (hTTR) and albumin (hALB). This model para-OH-TB-DiPhOBz was found to be capable of competing with thyroxine (T4) for the binding site on hTTR and hALB. In silico analyses were also conducted using a 3D homology model for gull TTR, to predict whether these TB-DiPhOBz-based compounds may also act as ligands for an avian TH transport protein despite evolutionary differences with hTTR. This analysis found all three TB-DiPhOBz analogues to be potential ligands for gull TTR and have similar binding efficacies to THs. Results indicate structure-related differences in binding affinities of these ligands and suggest there is potential for these contaminants to interact with both mammalian and avian thyroid function.

A refined ecological risk assessment for California red-legged frog, Delta smelt, and California tiger salamander exposed to malathion.

The California red-legged frog (CRLF), Delta smelt (DS), and California tiger salamander (CTS) are 3 species listed under the United States Federal Endangered Species Act (ESA), all of which inhabit aquatic ecosystems in California. The US Environmental Protection Agency (USEPA) has conducted deterministic screening-level risk assessments for these species potentially exposed to malathion, an organophosphorus insecticide and acaricide. Results from our screening-level analyses identified potential risk of direct effects to DS as well as indirect effects to all 3 species via reduction in prey. Accordingly, for those species and scenarios in which risk was identified at the screening level, we conducted a refined probabilistic risk assessment for CRLF, DS, and CTS. The refined ecological risk assessment (ERA) was conducted using best available data and approaches, as recommended by the 2013 National Research Council (NRC) report "Assessing Risks to Endangered and Threatened Species from Pesticides." Refined aquatic exposure models including the Pesticide Root Zone Model (PRZM), the Vegetative Filter Strip Modeling System (VFSMOD), the Variable Volume Water Model (VVWM), the Exposure Analysis Modeling System (EXAMS), and the Soil and Water Assessment Tool (SWAT) were used to generate estimated exposure concentrations (EECs) for malathion based on worst-case scenarios in California. Refined effects analyses involved developing concentration-response curves for fish and species sensitivity distributions (SSDs) for fish and aquatic invertebrates. Quantitative risk curves, field and mesocosm studies, surface-water monitoring data, and incident reports were considered in a weight-of-evidence approach. Currently, labeled uses of malathion are not expected to result in direct effects to CRLF, DS or CTS, or indirect effects due to effects on fish and invertebrate prey. Integr Environ Assess Manag 2018;14:224-239. © 2017 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals, Inc. on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Optimization of an in vitro assay methodology for competitive binding of thyroidogenic xenobiotics with thyroxine on human transthyretin and albumin.

Thyroid hormones (THs) are involved in the regulation of many physiological processes in vertebrates. Competition for TH binding sites on serum transport proteins can interfere with delivery of THs to target tissues, and this is a potential mechanism of action of exogenous thyroidogenic substances. To date, detailed accounts of in vitro methods for competitive binding with THs on TH transport proteins (human or wildlife) are sparse. In the limited number of published studies on in vitro radio-labelled TH-TH transport protein interactions, method descriptions were brief and with insufficient details for successful replication. Furthermore, upon review of these methodologies, we identified several opportunities for optimization. The present study addresses the methodological deficiencies and describes, in detail, a fully optimized and validated competitive T4 radio-ligand binding assay with human transthyretin (TTR) and albumin (ALB). •Significant improvements were made over previous methods, including better maintenance of protein stability and enhanced measurement of competition between different ligands.•Sample size was reduced to allow use of small pre-packed size exclusion chromatography columns, which eliminates the rinsing step during the separation procedure.•The assay was parameterized for use with T4 and human TTR and ALB.